CHMP4A

UniProt ID: Q9BY43
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

CHMP4A encodes a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4A-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and downstream endolysosomal degradation. CHMP4A also participates in autophagy/autophagosome contexts, plasma membrane repair, cytokinetic abscission, nuclear envelope repair, and viral budding as topologically related ESCRT output contexts, but those should not obscure the core ESCRT-III membrane-remodeling role.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005635 nuclear envelope
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear envelope.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031468 nuclear membrane reassembly
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex
IBA
GO_REF:0000033
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0009898 cytoplasmic side of plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0032511 late endosome to vacuole transport via multivesicular body sorting pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome to vacuole transport via multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0000776 kinetochore
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0001778 plasma membrane repair
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.
Reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments.
Supporting Evidence:
PMID:24482116
ESCRT proteins were recruited within seconds to plasma membrane wounds
PMID:24482116
repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005643 nuclear pore
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear pore.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005765 lysosomal membrane
IEA
GO_REF:0000117
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005828 kinetochore microtubule
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0007034 vacuolar transport
IEA
GO_REF:0000002
MODIFY
Summary: The broad vacuolar transport label is less precise than CHMP4A MVB/endosomal sorting function.
Reason: CHMP4A is best represented by ESCRT-III-mediated MVB sorting and ILV/membrane fission, not generic vacuolar transport.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0007080 mitotic metaphase chromosome alignment
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030496 midbody
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: midbody.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030659 cytoplasmic vesicle membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: cytoplasmic vesicle membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0031468 nuclear membrane reassembly
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031902 late endosome membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: late endosome membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0032585 multivesicular body membrane
IEA
GO_REF:0000117
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0036258 multivesicular body assembly
IEA
GO_REF:0000117
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0039702 viral budding via host ESCRT complex
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0042803 protein homodimerization activity
IEA
GO_REF:0000117
MODIFY
Summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IEA
GO_REF:0000117
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0046761 viral budding from plasma membrane
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0061952 midbody abscission
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: midbody abscission.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0071985 multivesicular body sorting pathway
IEA
GO_REF:0000117
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0097352 autophagosome maturation
IEA
GO_REF:0000117
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1901673 regulation of mitotic spindle assembly
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1902774 late endosome to lysosome transport
IEA
GO_REF:0000117
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1904930 amphisome membrane
IEA
GO_REF:0000117
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding
IPI
PMID:16730941
A systematic analysis of human CHMP protein interactions: ad...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding
IPI
PMID:17350572
Structural and biochemical studies of ALIX/AIP1 and its role...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding
IPI
PMID:18511562
ALIX-CHMP4 interactions in the human ESCRT pathway.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0000421 autophagosome membrane
IDA
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome membrane.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000776 kinetochore
IDA
PMID:26040712
Spastin and ESCRT-III coordinate mitotic spindle disassembly...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex
NAS
PMID:36107470
Comprehensive analysis of the human ESCRT-III-MIT domain int...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0001778 plasma membrane repair
IDA
PMID:24482116
ESCRT machinery is required for plasma membrane repair.
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane repair.
Reason: Plasma membrane repair is a valid ESCRT output context, but the core CHMP4A function remains ESCRT-III membrane remodeling in endosomal/MVB and related compartments.
Supporting Evidence:
PMID:24482116
ESCRT proteins were recruited within seconds to plasma membrane wounds
PMID:24482116
repair of certain wounds is ensured by ESCRT-mediated extracellular shedding of wounded portions
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005643 nuclear pore
IDA
PMID:26040713
ESCRT-III controls nuclear envelope reformation.
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear pore.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005765 lysosomal membrane
IDA
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: lysosomal membrane.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005828 kinetochore microtubule
IDA
PMID:26040712
Spastin and ESCRT-III coordinate mitotic spindle disassembly...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: kinetochore microtubule.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005886 plasma membrane
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0006914 autophagy
IMP
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagy.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0006997 nucleus organization
IMP
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosom...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nucleus organization.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0007080 mitotic metaphase chromosome alignment
IMP
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosom...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: mitotic metaphase chromosome alignment.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0030496 midbody
IDA
PMID:26040712
Spastin and ESCRT-III coordinate mitotic spindle disassembly...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: midbody.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0031468 nuclear membrane reassembly
IMP
PMID:26040713
ESCRT-III controls nuclear envelope reformation.
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nuclear membrane reassembly.
Reason: Nuclear envelope or nuclear pore repair/reassembly is a supported ESCRT-III context but is secondary to CHMP4A core ESCRT-III membrane-remodeling function.
Supporting Evidence:
PMID:26040713
ESCRT-III controls nuclear envelope reformation
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0032585 multivesicular body membrane
IDA
PMID:16554368
The ESCRT-III subunit hVps24 is required for degradation but...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0036258 multivesicular body assembly
NAS
PMID:16505166
Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0039702 viral budding via host ESCRT complex
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
IDA
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0046761 viral budding from plasma membrane
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding from plasma membrane.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0051469 vesicle fusion with vacuole
NAS
PMID:16505166
Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...
MODIFY
Summary: vesicle fusion with vacuole overstates a direct vesicle-fusion role for CHMP4A.
Reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0061763 multivesicular body-lysosome fusion
NAS
PMID:16505166
Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a...
MODIFY
Summary: multivesicular body-lysosome fusion overstates a direct vesicle-fusion role for CHMP4A.
Reason: CHMP4A is an ESCRT-III membrane-remodeling subunit in MVB/endolysosomal trafficking; cached evidence supports late endosome/MVB to lysosome traffic more directly than CHMP4A as a fusion effector.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0061952 midbody abscission
IMP
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosom...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: midbody abscission.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0071985 multivesicular body sorting pathway
IDA
PMID:16554368
The ESCRT-III subunit hVps24 is required for degradation but...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0090148 membrane fission
NAS
PMID:19234443
Membrane scission by the ESCRT-III complex.
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane fission.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0097352 autophagosome maturation
IMP
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: autophagosome maturation.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1901673 regulation of mitotic spindle assembly
IMP
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosom...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: regulation of mitotic spindle assembly.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1902774 late endosome to lysosome transport
IMP
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: late endosome to lysosome transport.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:1904930 amphisome membrane
IDA
PMID:17984323
Functional multivesicular bodies are required for autophagic...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: amphisome membrane.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0050877 nervous system process
IMP
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nervous system process.
Reason: The neuron paper supports CHMP4A-dependent neuronal survival and cargo turnover, but nervous system process is a broad phenotype rather than CHMP4A core molecular/cellular function.
Supporting Evidence:
PMID:21975012
hSnf7-1 and hSnf7-2 are required for the survival of human neurons
PMID:21975012
hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
GO:0071985 multivesicular body sorting pathway
IMP
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body sorting pathway.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0000815 ESCRT III complex
IDA
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0042802 identical protein binding
IPI
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
MODIFY
Summary: identical protein binding captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0051258 protein polymerization
IMP
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0005515 protein binding
IPI
PMID:18641129
Differential requirements for Alix and ESCRT-III in cytokine...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0016236 macroautophagy
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
ACCEPT
Summary: Supported PN-relevant autophagy/endolysosomal CHMP4A context: macroautophagy.
Reason: CHMP4A/Snf7-1 depletion causes autophagosome accumulation in human neurons, and ESCRT/MVB function is required for autophagic degradation; this supports retaining autophagy and autophagosome-context annotations without claiming CHMP4A alone was directly assayed as the phagophore-sealing effector.
Supporting Evidence:
PMID:21975012
SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
PMID:17984323
Functional multivesicular bodies are required for autophagic clearance
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0036258 multivesicular body assembly
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: multivesicular body assembly.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0039702 viral budding via host ESCRT complex
TAS
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's a...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0000815 ESCRT III complex
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0005737 cytoplasm
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasm.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005768 endosome
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: endosome.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
GO:0005886 plasma membrane
IDA
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0010324 membrane invagination
IMP
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane invagination.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0030117 membrane coat
IMP
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: membrane coat.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0051258 protein polymerization
IMP
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationsh...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: protein polymerization.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0039702 viral budding via host ESCRT complex
IGI
PMID:24107264
ESCRT requirements for EIAV budding.
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: viral budding via host ESCRT complex.
Reason: Viral budding is directly supported as ESCRT hijacking but is not an endogenous core CHMP4A proteostasis function.
Supporting Evidence:
PMID:18511562
ALIX protein must bind and recruit CHMP4 subunits of the ESCRT-III complex
PMID:24878737
Structure of cellular ESCRT-III spirals and their relationship to HIV budding
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0005515 protein binding
IPI
PMID:14519844
Divergent retroviral late-budding domains recruit vacuolar p...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0042803 protein homodimerization activity
IPI
PMID:14519844
Divergent retroviral late-budding domains recruit vacuolar p...
MODIFY
Summary: protein homodimerization activity captures CHMP4A self-association but is less accurate than ESCRT-III polymerization and membrane bending.
Reason: CHMP4A forms curved ESCRT-III filaments/polymers that bend membranes; homodimer or identical-protein binding terms are weaker molecular descriptions.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
GO:0005515 protein binding
IPI
PMID:14505570
The protein network of HIV budding.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0000815 ESCRT III complex
IDA
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: ESCRT III complex.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
PMID:18209100
Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0005515 protein binding
IPI
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for CHMP4A: protein binding.
Reason: CHMP4A has real ESCRT, ALIX, Borealin, VPS4, and high-throughput interactions, but the curated function should describe ESCRT-III polymerization, membrane bending/fission, and specific ESCRT-complex contexts rather than plain protein binding.
Supporting Evidence:
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
PMID:18511562
Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4 proteins (CHMP4A-C)
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0005634 nucleus
IDA
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: nucleus.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005737 cytoplasm
IDA
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasm.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane
IMP
PMID:21975012
ESCRT-III subunits Snf7-1 and Snf7-2 differentially regulate...
REMOVE
Summary: The cited CHMP4A neuron paper does not support post-translational targeting to the ER membrane.
Reason: PMID:21975012 supports CHMP4A/Snf7-1 in neuron survival, ESCRT-III cargo turnover, and autophagosome accumulation; it does not provide evidence that CHMP4A mediates ER membrane targeting.
Supporting Evidence:
PMID:21975012
hSnf7-1 and hSnf7-2 are required for the survival of human neurons
PMID:21975012
hSnf7-1 and hSnf7-2 may have preferred interacting partners to form distinct ESCRT-III with different cellular functions
GO:0006900 vesicle budding from membrane
IMP
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0006900 vesicle budding from membrane
IGI
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
ACCEPT
Summary: Supported core CHMP4A ESCRT-III/MVB membrane-remodeling annotation: vesicle budding from membrane.
Reason: CHMP4A is a core ESCRT-III/Snf7-family subunit that polymerizes on endosomal and MVB membranes to promote membrane budding/fission and MVB cargo sorting.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)
GO:0009898 cytoplasmic side of plasma membrane
IDA
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytoplasmic side of plasma membrane.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0051117 ATPase binding
IPI
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: ATPase binding.
Reason: ATPase binding reflects VPS4 engagement with CHMP4A filaments and is useful context, but CHMP4A itself is the ESCRT-III polymerizing membrane-remodeling subunit.
Supporting Evidence:
PMID:18209100
Binding to a coexpressed adenosine triphosphate hydrolysis-deficient mutant of VPS4B draws these filaments together
UniProt:Q9BY43
Interacts with VPS4A
GO:0097320 plasma membrane tubulation
IMP
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.
Reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0097320 plasma membrane tubulation
IGI
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: plasma membrane tubulation.
Reason: Plasma membrane tubulation is a useful overexpression/model phenotype for CHMP4A filament curvature, not the normal core biological process.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
UniProt:Q9BY43
Cytoplasmic vesicle membrane. Late endosome membrane
UniProt:Q9BY43
Membrane-associated
GO:0005829 cytosol
TAS
Reactome:R-HSA-3159232
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-917693
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-917700
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668389
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668395
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668398
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668405
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668415
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0005829 cytosol
TAS
Reactome:R-HSA-9668419
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: cytosol.
Reason: This location or output context is supported or plausible for CHMP4A but is broad or secondary relative to its core ESCRT-III MVB/endosomal membrane-remodeling role.
Supporting Evidence:
PMID:21975012
Both hSnf7-1 and hSnf7-2 were expressed in human postmitotic neurons and seemed to be present in both the nucleus and cytoplasm
GO:0030496 midbody
IDA
PMID:22724069
The chromosomal passenger complex controls the function of e...
KEEP AS NON CORE
Summary: True or plausible non-core CHMP4A ESCRT context: midbody.
Reason: Cytokinesis/midbody and spindle annotations are supported ESCRT output contexts, but they are not the central endolysosomal/proteostasis function emphasized for CHMP4A.
Supporting Evidence:
PMID:22724069
Borealin interacts directly with the Snf7 components of ESCRT-III
PMID:22724069
controls abscission timing through inhibition of ESCRT-III Snf7 polymerization
UniProt:Q9BY43
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
UniProt:Q9BY43
involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
GO:0180020 membrane bending activity
IDA
PMID:18209100
Plasma membrane deformation by circular arrays of ESCRT-III ...
NEW
Summary: New CHMP4A molecular-function annotation supported by direct ESCRT-III filament/membrane curvature evidence.
Reason: PMID:18209100 directly shows CHMP4A/hSnf7-1-containing ESCRT-III filaments promote or stabilize negative membrane curvature and outward budding, making membrane bending activity more informative than generic protein binding.
Supporting Evidence:
UniProt:Q9BY43
believed to mediate the necessary vesicle extrusion and/or membrane fission activities
PMID:18209100
form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
PMID:19234443
ESCRT-III has the instrinsic ability to drive the scission of membrane necks
PMID:18209100
assemble into regular approximately 5-nm filaments that curve and self-associate
PMID:18209100
proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)

Core Functions

CHMP4A/Snf7-1 is a core ESCRT-III structural subunit that polymerizes into curved membrane-associated filaments and promotes or stabilizes negative membrane curvature for reverse-topology budding/fission.

Supporting Evidence:
  • UniProt:Q9BY43
    believed to mediate the necessary vesicle extrusion and/or membrane fission activities
  • PMID:18209100
    form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding
  • PMID:19234443
    ESCRT-III has the instrinsic ability to drive the scission of membrane necks
  • PMID:18209100
    assemble into regular approximately 5-nm filaments that curve and self-associate
  • PMID:18209100
    proteins hSnf7-1 (CHMP4A) and hSnf7-2 (CHMP4B)

CHMP4A-containing ESCRT-III assemblies mediate MVB intraluminal vesicle formation and ubiquitin-dependent endosomal cargo sorting toward endolysosomal degradation.

Supporting Evidence:
  • UniProt:Q9BY43
    Probable core component of the endosomal sorting required for transport complex III (ESCRT-III)
  • UniProt:Q9BY43
    involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs
  • PMID:18209100
    ESCRT-III polymers delineate and help generate the luminal vesicles of multivesicular bodies
  • PMID:18209100
    Multivesicular bodies (MVBs) are mid-stage endosomes that contain intraluminal vesicles

CHMP4A/Snf7-1 contributes to autophagy/autophagosome maturation contexts as part of ESCRT-dependent endolysosomal membrane remodeling; direct human-neuron knockdown causes autophagosome accumulation.

Supporting Evidence:
  • PMID:21975012
    SiRNA knockdown of hSnf7-1 in human neurons leads to autophagosome accumulation
  • PMID:17984323
    Functional multivesicular bodies are required for autophagic clearance

References

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Suggested Questions for Experts

Q: Which CHMP4 paralog, CHMP4A, CHMP4B, or CHMP4C, is the dominant Snf7-family subunit during human phagophore closure and autophagosome maturation?

Q: Should GO annotations distinguish direct CHMP4A membrane-bending/polymer function from broader ESCRT output processes such as viral budding, plasma membrane repair, and nuclear envelope sealing?

Q: Does CHMP4A preferentially pair with CHMP2A in autophagy and endosomal cargo sorting, as suggested by human-neuron cargo turnover assays?

Suggested Experiments

Experiment: Use endogenous CHMP4A tagging and acute CHMP4A depletion/rescue during starvation-induced autophagy to image recruitment to phagophores, autophagosomes, and amphisomes.

Hypothesis: If CHMP4A directly participates in autophagosome maturation or closure, it should be transiently recruited to autophagy membranes and rescue should require its polymerization/membrane-binding region.

Experiment: Compare wild-type CHMP4A with ALIX-binding and C-terminal autoinhibition mutants in MVB cargo sorting, ESCRT spiral formation, plasma membrane repair, and viral budding assays.

Hypothesis: CHMP4A polymerization and partner recruitment requirements differ across endogenous ESCRT outputs and virus-hijacked budding.

Experiment: Biochemically reconstitute CHMP4A-containing human ESCRT-III polymers with CHMP2A/CHMP3/VPS4 and test membrane bending/scission on defined liposomes.

Hypothesis: CHMP4A contributes Snf7-family filament curvature that can drive membrane bending and support reverse-topology scission in a minimal human ESCRT-III module.

πŸ“š Additional Documentation

Notes

(CHMP4A-notes.md)

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Pn Notes

(CHMP4A-pn-notes.md)

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